Accumulation of adenine DNA glycosylase-sensitive sites in human mitochondrial DNA

Kenichi Miyako, Chihiro Takamatsu, Shuyo Umeda, Tatsurou Tajiri, Masato Furuichi, Yusaku Nakabeppu, Mutsuo Sekiguchi, Naotaka Hamasaki, Koichiro Takeshige, Dongchon Kang

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The mitochondrial respiratory chain inevitably produces reactive oxygen species as byproducts of aerobic ATP synthesis. Mitochondrial DNA (mtDNA), which is located close to the respiratory chain, is reported to contain much more 8-oxoguanine (8-oxoG), an oxidatively modified guanine base, than nuclear DNA. Despite such a high amount of 8-oxoG in mtDNA (1-2 8-oxoG/104 G), mtDNA is barely cleaved by an 8-oxoG DNA glycosylase or MutM, which specifically excises 8-oxoG from a C:8-oxoG pair. We find here that about half of human mtDNA molecules are cleaved by another 8-oxogG-recognizing enzyme, an adenine DNA glycosylase or MutY, which excises adenine from an A:8-oxoG pair. The cleavage sites are mapped to adenines. The calculated number of MutY-sensitive sites in mtDNA is approximately 1.4/104. This value roughly corresponds with the electrochemically measured amount of 8-oxoG in mtDNA (2.2/104), raising the possibility that 8-oxoG mainly accumulates as an A:8-oxoG pair.

Original languageEnglish
Pages (from-to)12326-12330
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number16
DOIs
Publication statusPublished - Apr 21 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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